While performing medical procedures as part of a surgical intervention or treatment of injury, a physician must often deal with extravasation of body fluids, such as cerebrospinal fluids during brain or spinal surgery, or blood resulting from an injury, a disease or disorder, or from a surgical procedure. Restoring tissue and circulation integrity is important for a positive outcome of a treatment regardless of whether the damage was the result of an injury or a surgical procedure.
The oldest method of joining damaged tissues is the use of mechanical fasteners such as clamps, staples or sutures. Mechanical tissue fasteners suffer from a variety of limitations. Mechanical fasteners require significant skill, are time consuming to apply and can leak along the line of joinder, which can itself cause additional trauma to surrounding tissue. Also, mechanical fasteners can be ineffective in a number of highly vascularized organs. These disadvantages further slow the surgical procedure and healing time.
Attempts to overcome these disadvantages have resulted in the development of adhesives, glues or sealants capable of bonding tissue surfaces together rapidly, either alone, or in combination with mechanical fastening while promoting, or at least not inhibiting, normal healing and reducing or preventing the loss of body fluids.
A common class of tissue adhesives is fibrin-based materials, which contain a concentrate of fibrinogen and thrombin. The fibrin adhesives are typically two-component adhesives that when mixed together with a calcium source react to simulate the last stages of the naturally occurring blood clot-forming cascade. The resulting clot adheres to tissue and bridges tissue, gaps and seals tissue until healing can occur. However, fibrin-based adhesives have met with limited success owing to low strength of the sealing materials and the risk associated with using human blood derived products which may be contaminated.
Glues based on gelatin cross-linked with an aldehyde have also met with limited success. Representative of this class of glues are gelatin-resorcinol cross-linked with formaldehyde (GRF) or glutaraldehyde (GRFG). While gelatin-based glues have been extensively studied and shown to generally be effective, these compositions have met with limited success owing to the use of hot gelatin solutions, tissue irritation associated with the aldehyde, and the criticality of the handling procedures needed to obtain proper cross-linking at the joinder site.
Due to the above-described limitations, considerable development effort has been directed towards finding a suitable synthetic composition which can be used as tissue glues or sealants. To this end, cyanoacrylates, polyurethanes, polymethylmethacrylates and polyethylene glycols, among other synthetic polymers, have been investigated as tissue glues or sealants with limited success. There are few available tissue glues or sealant compositions that meet the requirements of sufficient mechanical strength and biocompatibility, in addition to handling properties consistent with a wide variety of surgical settings.
However, these compositions show disadvantages with regard to handling and mechanical properties such as swelling of the biomaterial. Thus, there exists a need for a biomaterial that can be applied as a tissue glue or sealant that is not only biocompatible, but also has a well-defined cure and shows a combination of the required mechanical properties.
It is therefore an object of the present invention to provide compositions, methods and kits suitable for forming synthetic biomaterials for use as tissue sealant.
It is a further object of the invention to provide a synthetic biomaterial for use as tissue sealant which presents low increase in volume owing to water uptake.
It is a further object of the invention to provide a synthetic biomaterial for use as tissue sealant which is completely resorbable over time.
It is a further object of the invention to provide a synthetic biomaterial with good mechanical strength for use as tissue sealant.
It is a further object of the invention to provide a synthetic biomaterial that can potentially serve as an adjunct to sutured dural repair during cranial surgery and reduces or prevents leakage of cerebrospinal fluid into the external environment.